Circadian variation in plasma theophylline concentrations during maintenance therapy with a sustained-release...

Circadian variation in plasma theophylline concentrations was studied in eight patients with obstructive airways disease during regular 12-hourly dosing at 09.00 and 21.00 h with a sustained-release theophylline formulation. After regular dosing for a minimum period of 3 days, plasma concentration measurements were made at 09.00, 13.00, 21.00 and 01.00 h on 3 consecutive days and at more regular intervals during a complete 24 h period on day 4. On each day, theophylline concentrations for the first 4 h of the dosing interval were consistently higher during the day than at night. However, the differences were significant only at 13.00/01.00 h on day 2, and for each of the first 4 h on day 4. On day 4, following the dose at 21.00 h the mean peak plasma theophylline concentration occurred 6.9 +/- 0.8 h after dosing; in contrast, after the morning dose the mean peak concentration occurred at 4.5 +/- 0.8 h. However, the mean 'steady-state' concentrations during the two dose intervals were not significantly different. Thus circadian variations in plasma drug concentrations do occur in patients taking maintenance theophylline therapy: differing rates of absorption may account for the observed pattern.